|Hao Jiang, Ph.D.
My lab studies roles of histone modifications, with a particular focus on histone H3K4 methylation, in the regulation of gene expression in stem cell fate determination.
The central properties of the embryonic stem cells lie in their continuous self-renewal while maintaining the potential to differentiate into all types of cells in the organism. It has recently been demonstrated that various types of differentiated cells can be reverted to the pluripotent state or can be converted to one another. Controlling the stability and plasticity of cell identity is obviously crucial for animal development and physiology, and is also pivotal for regenerative medicine. With a few exceptions, all cells in an organism share the same genome, but they do have different epigenomes and gene expression patterns. Therefore, at the heart of the cell identity control is the control of gene expression. Epigenetic mechanisms including the covalent chemical modifications on histones are increasingly recognized as a fundamental and prevalent means to regulate gene expression. In a simplistic view, histone H3K4 methylation is generally associated with gene activation, while H3K27 methylation with gene repression. However, it is still difficult today to give definitive answers to some simple yet fundamental questions including: Is H3K4 methyl mark functionally critical for transcription? If yes, then to what extent does it impact on animal physiology?
My postdoctoral work has shown that Dpy-30, a conserved common subunit of MLL family complexes (the major H3K4 methyltransferases in mammals), plays an essential functional role in priming the developmental genes for efficient induction during ES cell fate specification (Jiang et al, Cell 2011). My recent work has also identified a novel factor associated with the Dpy-30/MLL complexes, and demonstrated its activity in modulating histone modification by the complexes, in co-activating chromatin transcription, and in mediating efficient gene induction upon ES cell fate transition (Jiang et al, unpublished).
Current and future research in the lab continues to focus on the epigenetic regulation of gene expression critically involved in stem cell fate determination. Using stem cells as a biological system, some of the projects include: (i) exploring mechanisms underlying the recruitment of specific histone methyltransferases to their target sites through a unique target identification system that has been recently established in the lab; and (ii) further characterization of the novel factor that is associated with Dpy-30/MLL complexes. Next-generation sequencing will be used to identify its target sites in the ES cell genome and this will likely give important information on how this factor may help regulate ES cell differentiation. Genetic approach will also be used to understand its physiological role in animal development.